Reduction of 2,5-diketogluconic acid

Abstract

The novel stereoselective and regioselective alkali metal borohydride reduction of 2,5-diketogluconic acid, alkyl esters or salts thereof to form 2-ketogulonic acid together with lesser amounts of 2-ketogluconic acid is disclosed. The 2-ketogulonic acid is readily converted to ascorbic acid.

What is claimed is: 
     
       1. A process for preparing a 2-ketogulonate and 2-ketogluconate mixture which comprises contacting a 2,5-diketogluconate with from about 0.8 to 1.1 equivalents per mole of an alkali metal borohydride in solution at a pH greater than 5 and a temperature between about -30° C. and 50° C., said 2,5-diketogluconate being selected from 2,5-diketogluconic acid, a normal alkyl ester of said acid wherein said alkyl group is of 1 to 4 carbon atoms, and a salt of said acid having a counterion selected from an alkali metal, an alkaline earth metal, ammonium and tetraalkylammonium having from 1 to 4 carbon atoms in each alkyl group. 
     
     
       2. The process of claim 1 wherein the contacting is conducted at a temperature of about -25° C. to +25° C. 
     
     
       3. The process of claim 1 wherein the contacting is conducted at a pH between about 6 and 10.5. 
     
     
       4. The process of claim 1 wherein said 2,5-diketogluconate is between about 5 and 20 weight percent of said solution. 
     
     
       5. The process of claim 1 wherein said alkali metal counterion is sodium. 
     
     
       6. The process of claim 1 wherein said alkaline earth metal counterion is calcium. 
     
     
       7. The process of claim 1 wherein said alkyl ester of 2,5-diketogluconic acid is methyl 2,5-diketogluconate. 
     
     
       8. The process of claim 1 wherein said tetra-alkyl ammonium counterion is tetra-methyl ammonium. 
     
     
       9. The process of claim 1 wherein said alkali metal borohydride is sodium borohydride. 
     
     
       10. The process of claim 1 wherein the contacting is conducted in aqueous solution. 
     
     
       11. The process of claim 10 wherein said aqueous solution contains a co-solvent selected from an alkanol of 1 to 4 carbon atoms, an alkanediol of 2 to 4 carbon atoms, acetonitrile, dimethyl sulfoxide and dimethyl formamide. 
     
     
       12. The process of claim 11 wherein said co-solvent is methanol. 
     
     
       13. The process of claim 1 wherein the contacting is conducted in the presence of a boron-complexing agent selected from an alkali metal fluoride, ammonium fluoride and a boron-absorbing ion-exchange resin. 
     
     
       14. The process of claim 1 wherein said mixture of the 2-ketogulonate and the 2-ketogluconate is contacted with an acid selected from hydrochloric acid, hydrobromic acid, sulfuric acid and sulfonic ion exchange resins at a temperature between about 50° C. and 130° C. until lactonization to ascorbic acid is substantially complete. 
     
     
       15. The process of claim 14 wherein said acid is hydrochloric acid. 
     
     
       16. The process of claim 15 wherein the temperature is from about 60° C. to 90° C.